Genome-Wide Association Study Using Individual Single-Nucleotide Polymorphisms and Haplotypes for Erythrocyte Traits in Alpine Merino Sheep

Abstract

Adaptation to high-altitude hypoxia is essential for domestic animals, such as yak, Tibetan chicken, and Tibetan sheep, living on high plateaus, as it ensures efficient oxygen absorption and utilization. Red blood cells are the primary medium for transporting oxygen in the blood. However, little is known about the genetic mechanism of erythrocyte traits. Genome-wide association studies (GWASs) based on single markers or haplotypes have identified potential mechanisms for genetic variation and quantitative traits. To identify loci associated with erythrocyte traits, we performed a GWAS based on the method of the single marker and haplotype in 498 Alpine Merino sheep for six erythrocyte traits: red blood cell count (RBC), hemoglobin (HGB), hematocrit (HCT), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), and RBC volume distribution width coefficient of variation (RWD_CV). Forty-two significant single-nucleotide polymorphisms (SNPs) associated with the six erythrocyte traits were detected by means of a single-marker GWAS, and 34 significant haplotypes associated with five erythrocyte traits were detected by means of haplotype analysis. We identified six genes (DHCR24, SPATA9, FLI1, PLCB1, EFNB2, and SH2B3) as potential genes of interest via gene function annotations, location, and expression variation. In particular, FLI1 and PLCB1 were associated with hematopoiesis and erythropoiesis, respectively. These results provide a theoretical basis for analyzing erythrocyte traits and high-altitude hypoxia adaptation in Alpine Merino sheep and will be a useful reference for future studies of plateau-dwelling livestock.

Genomic signatures of high-altitude adaptation and chromosomal polymorphism in geladas

“…tified several that have been identified as candidate genes in human hypoxia-adapted populations, including FRAS1, which is involved in renal agenesis and exhibits signatures of positive selection in Tibetans [60] and Ethiopians [61], HMBS, which is involved in heme biosynthesis and exhibits a signature of positive selection in Nepalese Sherpa [62], and TNRC18, a largely unknown gene that is linked to selection in Bajau breathhold divers [63]. Other notable candidate genes include AQP1, which plays an important role in fluid clearance and edema formation following acute lung injury [64], COX15, which is involved in heme a biosynthesis and cytochrome c oxidase assembly [65] and exhibits signatures of positive selection in high-altitude rhesus macaques [66], DHCR24, which is involved in the induction of heme oxygenase 1 (HO-1) [67] and exhibits a signature of positive selection in alpine sheep [68], and CYGB, which is part of the globin family and encodes an oxygen-binding respiratory protein [69].…”

Evaluation of Bayesian alphabet and GBLUP based on different marker density for genomic prediction in Alpine Merino sheep

“…As the object of this study, the Alpine Merino sheep has Australian Merino and Tibetan sheep lineage. Thanks to their adaptation in high-altitude hypoxia and excellent wool quality, they quickly adapted to the freezing Qinghai-Tibet Plateau, living in high altitude and cold conditions for generations ( Zhu et al 2020 ). The length and strength of the staple and fiber diameter (FD) are closely related to the wool quality and are the important economic traits of fine-wool sheep.…”

High-altitude adaptation and incipient speciation in geladas

“…tified several that have been identified as candidate genes in human hypoxia-adapted populations, including FRAS1, which is involved in renal agenesis and exhibits signatures of positive selection in Tibetans [60] and Ethiopians [61], HMBS, which is involved in heme biosynthesis and exhibits a signature of positive selection in Nepalese Sherpa [62], and TNRC18, a largely unknown gene that is linked to selection in Bajau breathhold divers [63]. Other notable candidate genes include AQP1, which plays an important role in fluid clearance and edema formation following acute lung injury [64], COX15, which is involved in heme a biosynthesis and cytochrome c oxidase assembly [65] and exhibits signatures of positive selection in high-altitude rhesus macaques [66], DHCR24, which is involved in the induction of heme oxygenase 1 (HO-1) [67] and exhibits a signature of positive selection in alpine sheep [68], and CYGB, which is part of the globin family and encodes an oxygen-binding respiratory protein [69].…”